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miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1)

Overview of attention for article published in Molecular Neurodegeneration, July 2016
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Title
miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1)
Published in
Molecular Neurodegeneration, July 2016
DOI 10.1186/s13024-016-0121-4
Pubmed ID
Authors

Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer, Jungsu Kim

Abstract

Loss-of-function mutations in PINK1 and PARKIN are the most common causes of autosomal recessive Parkinson's disease (PD). PINK1 is a mitochondrial serine/threonine kinase that plays a critical role in mitophagy, a selective autophagic clearance of damaged mitochondria. Accumulating evidence suggests mitochondrial dysfunction is one of central mechanisms underlying PD pathogenesis. Therefore, identifying regulatory mechanisms of PINK1 expression may provide novel therapeutic opportunities for PD. Although post-translational stabilization of PINK1 upon mitochondrial damage has been extensively studied, little is known about the regulation mechanism of PINK1 at the transcriptional or translational levels. Here, we demonstrated that microRNA-27a (miR-27a) and miR-27b suppress PINK1 expression at the translational level through directly binding to the 3'-untranslated region (3'UTR) of its mRNA. Importantly, our data demonstrated that translation of PINK1 is critical for its accumulation upon mitochondrial damage. The accumulation of PINK1 upon mitochondrial damage was strongly regulated by expression levels of miR-27a and miR-27b. miR-27a and miR-27b prevent mitophagic influx by suppressing PINK1 expression, as evidenced by the decrease of ubiquitin phosphorylation, Parkin translocation, and LC3-II accumulation in damaged mitochondria. Consequently, miR-27a and miR-27b inhibit lysosomal degradation of the damaged mitochondria, as shown by the decrease of the delivery of damaged mitochondria to lysosome and the degradation of cytochrome c oxidase 2 (COX2), a mitochondrial marker. Furthermore, our data demonstrated that the expression of miR-27a and miR-27b is significantly induced under chronic mitophagic flux, suggesting a negative feedback regulation between PINK1-mediated mitophagy and miR-27a and miR-27b. We demonstrated that miR-27a and miR-27b regulate PINK1 expression and autophagic clearance of damaged mitochondria. Our data further support a novel negative regulatory mechanism of PINK1-mediated mitophagy by miR-27a and miR-27b. Therefore, our results considerably advance our understanding of PINK1 expression and mitophagy regulation and suggest that miR-27a and miR-27b may represent potential therapeutic targets for PD.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Luxembourg 1 2%
Unknown 61 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 30%
Student > Master 11 17%
Researcher 9 14%
Student > Bachelor 4 6%
Professor > Associate Professor 3 5%
Other 5 8%
Unknown 12 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 25%
Neuroscience 14 22%
Agricultural and Biological Sciences 12 19%
Medicine and Dentistry 3 5%
Psychology 1 2%
Other 2 3%
Unknown 15 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 November 2017.
All research outputs
#7,575,720
of 12,122,714 outputs
Outputs from Molecular Neurodegeneration
#397
of 529 outputs
Outputs of similar age
#147,613
of 266,479 outputs
Outputs of similar age from Molecular Neurodegeneration
#18
of 20 outputs
Altmetric has tracked 12,122,714 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 529 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 16th percentile – i.e., 16% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,479 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.